The inverse association between HDL concentrations and coronary artery disease (CAD) risk has prompted a search for hygienic factors which elevate HDL levels. Physical activity is an attractive area for intervention since endurance athletes demonstrate HDL levels 10-20 mg/dl higher than their sedentary counterparts. Exercise training in previously sedentary subjects, however, has demonstrated a much more modest exercise effect, and the mechanism by which physical activity increases HDL levels is not defined. We hypothesize that exercise augments the transfer of lipids from lower density lipoproteins to HDL and that this lipid enrichment retards HDL degradation. The proposed studies will examine this hypothesis. We will compare HDL metabolism and fat tolerance in active distance runners and sedentary men under controlled dietary conditions. We will also examine the effects of two years of exercise training with or without weight loss on HDL metabolism in previously inactive men. Parameters of HDL metabolism including apoprotein synthetic and catabolic rates will be measured using radiolabelled HDL. HDL cholesterol and apoprotein concentrations, the ultracentrifugal distribution of HDL lipids, and the activity of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma will be quantified. The clearance of intravenous fat will be measured as an index of fat tolerance. Questions which we will address include: Do initial HDL levels determine the change in HDL with exercise training? What is the magnitude of the exercise effect? Are exercise- induced changes in HDL magnified by concurrent weight loss? How does exercise training alter HDL metabolism? This research should provide insight into factors regulating HDL levels and the metabolic alterations produced by physical activity. Because of the inverse association between HDL and coronary artery risk, the results may also suggest strategies for CAD prevention.